Unexplained Immunodeficiency and Opportunistic Infections in
Infants -- New York, New Jersey, California

CDC has received reports of four infants (under 2 years of age)
with unexplained cellular immunodeficiency and opportunistic
infections.

Case 1: The infant, a black/hispanic male weighing 5 lb 14 oz,
was born in December 1980 following a 36-38-week pregnancy.
Pregnancy
had been complicated by bleeding in the fourth month and by
preeclampsia in the ninth month. The infant was well until 3
months
of age, when oral candidiasis was noted. At 4 months,
hepatosplenomegaly was observed, and at 7 months, he had
staphylococcal impetigo. Growth, which had been slow, stopped at 9
months. Head circumference, which had been below the third
percentile, also stopped increasing. At 9 months, serum levels of
IgG
and IgA were normal; IgM was high-normal. T-cell studies were
normal,
except for impaired in-vitro responses to Candida antigen and
alloantigen.

At 17 months of age, the infant had progressive pulmonary
infiltrates, as well as continuing oral candidiasis, and was
hospitalized. Mycobacterium avium-intracellulare was cultured from
sputum and bone marrow samples. A CAT scan of the head revealed
bilateral calcifications of the basal ganglia and subcortical
regions
of the frontal lobes. Repeat immunologic studies done at age 20
months showed lymphopenia, decreased numbers of T-lymphocytes, and
severely impaired T-cell function in vitro; immunoglobulin
determinations are pending. The infant remains alive and is
receiving
therapy for his mycobacterial infection.

The infant's mother, a 29-year-old resident of New York City,
gave
a history of intravenous drug abuse. Although she was in
apparently
good health at the time of the infant's birth, she developed fever,
dyspnea, and oral candidiasis in October 1981. One month later,
she
was hospitalized and died of biopsy-proven Pneumocystis carinii
pneumonia (PCP). She had been lymphopenic during the
hospitalization;
further immunologic studies were not done. At autopsy, no
underlying
cause for immune deficiency was found.

Case 2: The infant, a Haitian male weighing 6 lb 11 oz, was
born
in January 1981 following full-term pregnancy. The immediate
postpartum period was complicated by respiratory distress.
Diarrhea
developed at 2 weeks of age and persisted. His physical
development
was retarded. At 5 months, he was hospitalized because of fever
and
diarrhea. On examination, he had hepatosplenomegaly,
lymphadenopathy,
and otitis media. While on antibiotics, he developed pulmonary
infiltrates. An open lung biopsy revealed Pneumocystis carinii,
Cryptococcus neoformans, and cytomegalovirus. Serum IgG, IgA, and
IgM
concentrations were elevated. The percentage of T-lymphocytes was
decreased, but T-cell response to mitogens was normal. The infant
died of respiratory insufficiency at 7H months of age. At autopsy,
the thymus, spleen, and lymph nodes showed lymphocyte depletion.
His
parents were residents of Brooklyn, New York; their health status
is
unknown.

Case 3: The infant, a Haitian male weighing 8 lb, was born in
November 1981 following a normal, full-term pregnancy. He was
apparently healthy until 5 months of age, when he was hospitalized
with fever and respiratory distress. On examination, he had
hepatosplenomegaly. A chest x-ray showed bilateral pulmonary
infiltrates. Despite antibiotic therapy, the infant's condition
deteriorated, and an open lung biopsy revealed PCP. Immunologic
studies showed elevated serum concentrations of IgG, IgA and IgM,
decreased percentage of T-lymphocytes, and impaired T-cell function
in
vitro. The infant died in May 1982. At autopsy, no cardiovascular
anomalies were seen; the thymus was hypoplastic, but all lobes were
present. His parents were residents of Newark, New Jersey; their
health status is unknown.

Case 4: The infant, a white female weighing 5 lb, was born in
April 1982 following a normal 35-week pregnancy. She was well
until 2
months of age, when oral and vaginal Candida infections were noted.
She responded to antifungal therapy, but at 5 months, candidiasis
recurred, and she had hepatosplenomegaly. Immunologic evaluation
showed that serum IgG, IgA, and IgM levels, normal at 2 months,
were
now elevated. The percentage of T-lymphocytes was decreased, and
lymphocyte response to alloantigen was impaired. At 6 months of
age,
the infant was hospitalized because of fever and cough. Open lung
biopsy revealed PCP. Despite appropriate antibiotic therapy, she
died
in November 1982.

The infant's mother, a 29-year-old resident of San Francisco,
is a
prostitute and intravenous drug abuser with a history of oral
candidiasis and mild lymphopenia. She has had two other female
children by different fathers. These half-sisters also have
unexplained cellular immunodeficiency; one died of PCP. The
children
had not lived together.

None of the four infants described in the case reports was
known
to have received blood or blood products before onset of illness.

Other cases with opportunistic infections: Six additional
young
children with opportunistic infections (five with PCP, one with M.
avium-intracellulare) and unusual cellular immunodeficiencies are
under investigation. Three are male. All six children have died.
One
was a half-sister of the infant in Case 4.

Other cases without opportunistic infections: Physicians from
New
York City, New Jersey, and California have reported another 12
young
children with immunodeficiencies similar to those seen in cases 1-4
but without life-threatening opportunistic infections. One is the
other half-sister of the infant in Case 4. All the children are
living; their ages range from 1 to 4 years. Eight are male.
Clinical
features seen in these 12 infants include: failure to thrive (83%),
oral candidiasis (50%), hepatosplenomegaly (92%), generalized
lymphadenopathy (92%), and chronic pneumonitis without a
demonstrable
infection (83%). Of the nine mothers for whom information is
available, seven are reported to be intravenous drug abusers. None
is
Haitian.
Reported by R O'Reilly, MD, D Kirkpatrick, MD, Memorial
Sloan-Kettering Cancer Center, C Butkus Small, MD, R Klein, MD, H
Keltz, MD, G Friedland, MD, Montefiore Hospital and Medical Center,
K
Bromberg, MD, S Fikrig, MD, H Mendez, MD, State University of New
York, Downstate Medical Center, A Rubinstein, MD, Albert Einstein
College of Medicine, M Hollander, MD, Misericordia Hospital Medical
Center, F Siegal, MD, Mt Sinai School of Medicine, J Greenspan, MD,
Northshore University Hospital, M Lange, MD, St Lukes-Roosevelt
Hospital Center, S Friedman, MD, New York City Dept of Health, R
Rothenberg, MD, State Epidemiologist, New York State Dept of
Health; J
Oleske, MD, C Thomas MD, R Cooper, MD, A de la Cruz, MD, St
Michaels
Medical Center, A Minefore, MD, St Josephs Medical Center, I
Guerrero,
MD, B Mojica, MD, W Parkin, DVM, State Epidemiologist, New Jersey
State Dept of Health; M Cowan, MD, A Ammann, MD, D Wara, MD,
University of California at San Francisco, S Dritz, MD, City/County
Health Dept, San Francisco, J Chin, MD, State Epidemiologist,
California State Dept of Health Svcs; Field Svcs Div, Epidemiology
Program Office, AIDS Activity, Div of Host Factors, Center for
Infectious Diseases, CDC, M Hammerschland, MD.

Editorial Note

Editorial Note: The nature of the immune dysfunction described in
the
four case reports is unclear. The infants lacked the congenital
anomalies associated with Di George's syndrome. The immunologic
features of high-normal or elevated immunoglobulin levels and
T-lymphocyte depletion are not typical of any of the well-defined
congenital immunodeficiency syndromes. They have, however, been
described in a few children with variants of Nezelof's syndrome, a
rare, poorly characterized illness of unknown etiology (1,2). The
occurrence of immune deficiency in the infant in case 4 and in her
half-sisters raises the possibility of an inherited disorder.
However, inheritance would have to have occurred in a dominant
manner,
an inheritance pattern not previously described for
immunodeficiency
resembling that seen in these half-sisters.

It is possible that these infants had the acquired immune
deficiency syndrome (AIDS). Although the mother of the infant in
case
1 was not studied immunologically, her death from PCP was probably
secondary to AIDS. The mothers of the other three infants were
Haitian or intravenous drug abusers, groups at increased risk for
AIDS
(3). The immunologic features described in the case reports
resemble
those seen both in adults with AIDS (4) and in a child reported to
have developed immunodeficiency following receipt of blood products
from a patient with AIDS (5). Case 2 had essentially normal T-cell
responses to mitogens in vitro. This finding is atypical for AIDS,
but it has been seen in a few adult AIDS cases (6).

Although the etiology of AIDS remains unknown, a series of
epidemiologic observations suggests it is caused by an infectious
agent (3,5,7-9). If the infants described in the four case reports
had AIDS, exposure to the putative "AIDS agent" must have occurred
very early. Cases 2-4 were less than 6 months old when they had
serious opportunistic infections. Case 1 had oral candidiasis
beginning at 3 months of age, although M. avium-intracellulare
infection was not documented until 17 months. Transmission of an
"AIDS agent" from mother to child, either in utero or shortly after
birth, could account for the early onset of immunodeficiency in
these
infants.

The relationship between the illnesses seen in the reported
cases
with severe opportunistic infection and the 12 infants without such
infections is unclear at present. The immune dysfuction seen in
the
children and the sociodemographic profiles of the mothers appear
similar in both groups. Prospective study of the 12 children is
necessary to define the natural history of their illnesses and the
possible relationship of their illnesses to AIDS.

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